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PubMed1999

Expression and activation of RAS and mitogen-activated protein kinases in macrophages treated in vitro with cisplatin: regulation by kinases, phosphatases and Ca2+/calmodulin.

Cisplatin (cis-dichlorodiammineplatinum II), a potent antitumour compound, stimulates immune responses by activating monocytes/macrophages and other cells of the immune system. However, the exact mechanism by which cisplatin activates these cells is poorly characterized and attempts are being made to understand this mechanism. Previous studies from this laboratory have shown that Lyn, a protein tyrosine kinase of the src family, and nuclear factor (NF)-kappaB are involved in cisplatin-induced macrophage activation. Recent studies suggest that the RAS and mitogen-activated protein (MAP) kinases function as a connecting link between activated lyn and NF-kB, which raises the possibility of their involvement in cisplatin-induced macrophage activation. Therefore, this study was undertaken to investigate the effect of cisplatin treatment on the expression/activation of RAS (a low molecular weight GTP-binding protein) and MAP kinases in murine peritoneal macrophages. The underlying mechanism of expression/activation of RAS and MAP kinases in cisplatin-treated macrophages was also investigated. Immunoblotting and immune-complex kinase assays revealed that cisplatin treatment of macrophages leads to increased expression/activation of RAS and MAP kinases, with optimal expression/activation at 15 min of treatment. Using a battery of specific inhibitor/modulators of different signalling molecules, this study shows that expression and activation of MAP kinases are two unrelated processes. It was also observed that kinase (protein tyrosine and protein kinase C) inhibitor and Ca2+/calmodulin antagonist inhibit expression/activation of RAS/MAP kinases in macrophages, whereas phosphatases (protein tyrosine and serine/threonine) inhibitor up-regulate these kinases.

Animals↗
PubMed2001

Drosophila as a focus in olfactory research: mapping of olfactory sensilla by fine structure, odor specificity, odorant receptor expression, and central connectivity.

This review intends to integrate recent data from the Drosophila olfactory system into an up-to-date account of the neuronal basis of olfaction. It focuses on (1) an electron microscopic study that mapped a large proportion of fruitfly olfactory sensilla, (2) large-scale electrophysiological recordings that allowed the classification of the odor response spectra of a complete set of sensilla, (3) the identification and expression patterns of candidate odorant receptors in the olfactory tissues, (4) central projections of neurons expressing a given odorant receptor, (5) an improved glomerular map of the olfactory center, and (6) attempts to exploit the larval olfactory system as a model of reduced cellular complexity. These studies find surprising parallels between the olfactory systems of flies and mammals, and thus underline the usefulness of the fruitfly as an olfactory model system. Both in Drosophila and in mammals, odorant receptor neurons appear to express only one type of receptor. Neurons expressing a given receptor are scattered in the olfactory tissues but their afferents converge onto a few target glomeruli only. This suggests that in both phyla, the periphery is represented in the brain as a chemotopic map. The major difference between mammals and fruitflies refers to the numbers of receptors, neurons, and glomeruli, which are largely reduced in the latter, and particularly in larvae. Yet, if activated in a combinatorial fashion, even this small set of elements could allow discrimination between a vast array of odorants.

Animals↗
PubMed1998

Cortical connections of the dorsomedial visual area in prosimian primates.

The dorsomedial visual area (DM) was originally identified in New World owl monkeys as an area rostral to dorsomedial visual area 2 (V2) that is heavily myelinated, contains a complete representation of the visual field, and has a unique distribution of connections with other visual areas. A DM homologue has been proposed in prosimian galagos on the basis of physiological mapping. We determined the pattern of connections of the proposed DM with other cortical visual areas in galagos by placing injections of several different neuroanatomical tracers into DM and locating the resulting label in relation to areal boundaries and modules by using architecture from cytochrome oxidase and myelin preparations. We found that DM is connected with V1, V2, the middle temporal area, and regions of the medial area, the middle superior temporal area, the dorsointermediate area, the ventral posterior area, and the ventral posterior parietal area. Following some injections, label was also found in the fundal superior temporal sulcus area and in the frontal eye field. Connections with V1 were patchy. Although the majority of labeled neurons were in cytochrome oxidase blobs of V1, many labeled neurons were located in interblob regions as well. Similarities in the connections and the architecture of DM of galagos and owl monkeys suggest that the same area has been identified in both groups of primates.

Amidines↗
PubMed1991

Electrocardiographic body surface potential mapping in the Wolff-Parkinson-White syndrome. Noninvasive determination of the ventricular insertion sites of accessory atrioventricular connections.

BACKGROUND: A reliable, noninvasive procedure to determine the location of accessory atrioventricular connections in patients with Wolff-Parkinson-White syndrome would add an important diagnostic tool to the clinical armamentarium. METHODS AND RESULTS: Body surface potential mapping (BSPM) using 180 electrodes in various-sized vests and displayed as a calibrated color map was used to determine the ventricular insertion site of the accessory atrioventricular (AV) connections in 34 patients with Wolff-Parkinson-White syndrome. Attempts were made to determine the 17 ventricular insertion sites described by Guiraudon et al. All 34 patients had an electrophysiologic study (EPS) at cardiac catheterization, and 18 had surgery so the ventricular insertion sites could be accurately located using EPS at surgery. A number of physiologic observations were also made with BSPM. CONCLUSIONS: The following conclusions were drawn: 1) BSPM using QRS analysis accurately predicts the ventricular insertion site of accessory AV connections in the presence of a delta wave in the electrocardiogram; 2) the ventricular insertion sites of accessory AV connections determined by BSPM and by EPS at surgery were identical or within one mapping site (1.5 cm or less) in all but four of 18 cases; three of the four exceptions had more than one accessory AV connection, and the other had a very broad ventricular insertion; 3) BSPM and EPS locations of the accessory AV connections correlated very well in the 34 cases despite the fact that BSPM determines the ventricular insertion site and EPS determines the atrial insertion site of the accessory AV connection; 4) as suggested by the three cases of multiple accessory AV connections, EPS and BSPM may be complementary since BSPM identified one pathway and EPS identified the other (in the case with a broad ventricular insertion, BSPM and EPS demonstrated different proportions of that insertion); 5) BSPM using ST-T analysis is very much less accurate in predicting the ventricular insertion site of accessory AV connections unless there is marked preexcitation; 6) standard electrocardiography using the Gallagher grid methodology (but with no attempt at stimulating maximal preexcitation) was not as accurate as QRS analysis of BSPM in predicting the ventricular insertion site of the accessory AV connection; however, exact comparison is hampered by the different number and size of the Gallagher and Guiraudon insertion sites; 7) BSPM using QRS analysis appears to be very accurate in predicting right ventricular versus left ventricular posteroseptal accessory AV connections; 8) typical epicardial right ventricular breakthrough, indicative of conduction via the specialized AV conduction system, occurs in all patients with left ventricular free wall accessory AV connections; 9) epicardial right ventricular breakthrough was not observed in cases with right ventricular free wall or anteroseptal accessory AV connections; 10) epicardial right ventricular breakthrough can occur in the presence of posteroseptal accessory AV connections, whether right or left ventricular; and 11) the delay in epicardial right ventricular breakthrough in cases with left ventricular insertion may provide a marker to estimate the degree of ventricular preexcitation.

Adult↗
PubMed2006

Enhanced excitatory synaptic connectivity in layer v pyramidal neurons of chronically injured epileptogenic neocortex in rats.

Formation of new recurrent excitatory circuits after brain injuries has been hypothesized as a major factor contributing to epileptogenesis. Increases in total axonal length and the density of synaptic boutons are present in layer V pyramidal neurons of chronic partial isolations of rat neocortex, a model of posttraumatic epileptogenesis. To explore the functional consequences of these changes, we used laser-scanning photostimulation combined with whole-cell patch-clamp recording from neurons in layer V of somatosensory cortex to map changes in excitatory synaptic connectivity after injury. Coronal slices were submerged in artificial CSF (23 degrees C) containing 100 microM caged glutamate, APV (2-amino-5-phosphonovaleric acid), and high divalent cation concentration to block polysynaptic responses. Focal uncaging of glutamate, accomplished by switching a pulsed UV laser to give a 200-400 micros light stimulus, evoked single- or multiple-component composite EPSCs. In neurons of the partially isolated cortex, there were significant increases in the fraction of uncaging sites from which EPSCs could be evoked ("hot spots") and a decrease in the mean amplitude of individual elements in the composite EPSC. When plotted along the cortical depth, the changes in EPSCs took place mainly between 150 and 200 microm above and below the somata, suggesting a specific enhancement of recurrent excitatory connectivity among layer V pyramidal neurons of the undercut neocortex. These changes may shift the balance within cortical circuits toward increased synaptic excitation and contribute to epileptogenesis.

2-Amino-5-phosphonovalerate↗
PubMed1997

Integration of local inputs in visual cortex.

In mammalian visual cortex, local connections are ubiquitous, extensively linking adjacent neurons of all types. In this study, optical maps of intrinsic signals and responses from single neurons were obtained from the same region of cat visual cortex while the effectiveness of the local cortical circuitry was altered by focally disinhibiting neurons within a column of known orientation preference. Maps of intrinsic signals indicated that local connections provide strong and functional subthreshold inputs to neighboring columns of other orientation preferences, altering the observed orientation preference to that of the disinhibited column. However, measuring the suprathreshold response using single-cell recordings revealed only mild changes of preferred orientation over the affected region. Because strongly tuned subthreshold inputs from cortex only marginally affect the tuning of a cortical cell's output, it is concluded that local cortical inputs are integrated weakly compared to geniculate inputs. Such circuitry potentially allows for the normalization of responses across a wide range of input activity through local averaging.

Animals↗
PubMed1991

A two-dimensional gel database of rat liver proteins useful in gene regulation and drug effects studies.

A standard two-dimensional (2-D) protein map of Fischer 344 rat liver (F344MST3) is presented, with a tabular listing of more than 1200 protein species. Sodium dodecyl sulfate (SDS) molecular mass and isoelectric point have been established, based on positions of numerous internal standards. This map has been used to connect and compare hundreds of 2-D gels of rat liver samples from a variety of studies, and forms the nucleus of an expanding database describing rat liver proteins and their regulation by various drugs and toxic agents. An example of such a study, involving regulation of cholesterol synthesis by cholesterol-lowering drugs and a high-cholesterol diet, is presented. Since the map has been obtained with a widely used and highly reproducible 2-D gel system (the Iso-Dalt system), it can be directly related to an expanding body of work in other laboratories.

Animals↗
PubMed1992

Subdivisions and connections of auditory cortex in owl monkeys.

The organization and connections of auditory cortex in owl monkeys, Aotus trivirgatus, were investigated by combining microelectrode mapping methods with studies of architecture and connections in the same animals. In most experiments, portions of auditory cortex were first explored with microelectrodes, neurons were characterized as responsive or not to auditory stimuli, and best frequencies were determined whenever possible. Most recordings were in cortex previously designated as primary (A-I) and rostral (R) auditory fields (Imig et al. J Comp Neurol 171:111, '77) and in a newly defined rostrotemporal field (RT) located rostral to R. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and fluorescent tracers were placed in electrophysiologically identified locations of A-I, R, and RT; the posterolateral (PL) and anterolateral (AL) divisions of a narrow belt of auditory cortex lateral and adjacent to A-I and R; cortex of the superior temporal gyrus lateral and rostrolateral to PL and AL; and regions of prefrontal cortex that receive inputs from auditory cortex. There were several major findings: 1. Best frequencies were most clearly determined for neurons within a densely myelinated strip of cortex on the lower bank and lip of the lateral sulcus. We divided this strip into three fields, A-I, R, and RT, although an alternative interpretation that A-I and R are parts of a single field remains tenable. In some cases, isofrequency contours appeared to continue uninterrupted across fields A-I and R, with lower frequencies represented laterally and higher frequencies represented deeper in the sulcus. In other cases, there was a tendency for high frequencies to be represented caudally and medially, and low frequencies laterally in A-I and rostrally in R, with partial discontinuity in the isofrequency contours. A reversal of the tonotopic gradient appeared in RT with a common low-frequency representation at the caudal border with R, and progressively higher frequencies encountered rostrally. Of the three fields, A-I appears slightly more myelinated than R, and RT slightly less than R. The distinctiveness of the three fields is further demonstrated by the patterns of connections. In particular, A-I and RT are both interconnected with R, but not with each other. Connections between A-I and R are between tonotopically matched locations. 2. A narrow 2-3 mm wide band of cortex lateral to A-I, R, and RT was also responsive to auditory stimuli, but typically neurons were more difficult to activate, and best frequencies were more difficult to determine. No distinctions in myeloarchitecture or CO activity were obvious.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1995

[Identification of motor area by transcranial magnetic stimulation using an "eight-figure" coil in patients with motor paralysis].

In patients with motor paralysis, we tried to identify the functional motor area by transcranial magnetic stimulation using an "eight-figure" coil designed by Ueno. Motor evoked potentials (MEPs) were recorded in 7 patients from 50 to 64 years old, and in 5 normal volunteers 26 to 45 years old. They were stimulated at 49 points over an unilateral hand motor area, and at 21 points over a foot motor area, and surface MEPs were recorded on their contralateral thenar muscle and abductor hallucis brevis muscle. In normal volunteers, the optimal eddy current for stimulating the hand motor area was directed anteriorly parallel to the midline, and for stimulating the foot motor area, it was postero-laterally directed with an angle of 45 degrees towards the midline. MEPs could be induced at their muscle contractions during which their thumbs and middle fingers softly touched each other, and their halluxes slightly flexed. In five patients two kinds of amplitude mappings reconstructed from MEPs were obtained at rest or at muscle contraction. A line connecting these two peaks on an amplitude mapping was regarded as an "MEP-motor area". A geographical difference between the MEP-motor area and MRI-motor area (identified by an MRI surface image) was studied at muscle contraction and at rest. In normal subjects the sites of the MEP-motor area and of the MRI-motor area coincided, whereas, in patients with space-occupying lesions near the central sulcus, the MEP-motor areas were located 1 to 2cm posterior to MRI-motor areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Preexcitation syndromes: surgical ablation therapy. The Cleveland Clinic experience.

Thirty-four patients with preexcitation syndrome had surgical ablation of the accessory atrioventricular connection. All presented with sustained symptomatic arrhythmias, which had resulted in syncope in seven patients and aborted sudden cardiac death in four. Arrhythmias induced at electrophysiologic evaluation included orthodromic reciprocating tachycardia in 32 patients, antidromic reciprocating tachycardia in five patients, and atrial fibrillation in 29 patients. A single accessory atrioventricular connection was located in 32 patients and two patients had multiple accessory connections. The accessory connection was located with intraoperative mapping in all patients and the pathway was successfully ablated in 32. Eleven patients underwent a transmural approach and 23 patients underwent an epicardial dissection. Cryotherapy was used in 22 patients. After a mean follow-up of 32 months, 28 patients were free from all arrhythmias without drug therapy. Six patients continued to have symptomatic arrhythmias but only one case was suspected to be secondary to unsuccessful ablation of the accessory connection. One patient with heart block induced at the surgical procedure is dependent upon a pacemaker.

Adolescent↗
PubMed1997

A multigene family encoding a diverse array of putative pheromone receptors in mammals.

The vomeronasal organ of mammals is an olfactory sensory structure that detects pheromones. It contains two subsets of sensory neurons that differentially express G alpha(o) and G alpha(i2). By comparing gene expression in single neurons, we identified a novel multigene family that codes for a diverse array of candidate pheromone receptors (VRs) expressed by the G alpha(o)+ subset. Different VRs are expressed by different neurons, but those neurons are interspersed, suggesting a distributed mode of sensory coding. Chromosome mapping experiments suggest an evolutionary connection between genes encoding VRs and receptors for volatile odorants. However, a dramatically different structure for VRs and the existence of variant VR mRNA forms indicate that there are diverse strategies to detect functionally distinct sensory stimuli.

Amino Acid Sequence↗
PubMed2006

Saccade-related spread of activity across superior colliculus may arise from asymmetry of internal connections.

The superior colliculus (SC) receives a retinotopic projection of the contralateral visual field in which the representation of the central field is expanded with respect to the peripheral field. The visual projection forms a nonlinear, approximately logarithmic, map on the SC. Models of the SC commonly assume that the function defining the strength of neuronal connections within this map (the kernel) depends only on the distance between two neurons, and is thus isotropic and homogeneous. However, if the connection strength is based on the distance between two stimuli in sensory space, the kernel will be asymmetric because of the nonlinear projection onto the brain map. We show, using a model of the SC, that one consequence of these asymmetric intrinsic connections is that activity initiated at one point spreads across the map. We compare this simulated spread with the spread observed experimentally around the time of saccadic eye movements with respect to direction of spread, differing effects of local and global inhibition, and the consequences of localized inactivation on the SC map. Early studies suggested that the SC spread was caused by feedback of eye displacement during a saccade, but subsequent studies were inconsistent with this feedback hypothesis. In our new model, the spread is autonomous, resulting from intrinsic connections within the SC, and thus does not depend on eye movement feedback. Other sensory maps in the brain (e.g., visual cortex) are also nonlinear and our analysis suggests that the consequences of asymmetric connections in those areas should be considered.

Algorithms↗
PubMed1988

Processing of thyrotropin-releasing hormone prohormone (pro-TRH) generates pro-TRH-connecting peptides. Identification and characterization of prepro-TRH-(160-169) and prepro-TRH-(178-199) in the rat nervous system.

Rat thyrotropin-releasing hormone prohormone (pro-TRH) contains five separate copies of the TRH progenitor sequence: Gln-His-Pro-Gly. Each of the five sequences is flanked by pairs of basic residues and linked together by one of several predicted connecting sequences. Two of the pro-TRH-connecting peptides, prepro-TRH-(160-169) and prepro-TRH-(178-199), were detected in extracts of rat neural tissues by radioimmunoassay using antibodies directed against the corresponding synthetic probes. Endogenous prepro-TRH-(160-169) and prepro-TRH-(178-199) were purified by gel exclusion chromatography, reverse-phase high pressure liquid chromatography, and ion-exchange chromatography. Structural identification of each peptide was achieved by chromatographic comparison with synthetic standards, immunological analysis, and tryptic mapping. Equimolar amounts of these connecting fragments were observed in hypothalamus and spinal cord. Quantification of TRH in spinal cord and hypothalamus extracts revealed the presence of 4.9-6.3 mol of TRH/mol of prepro-TRH-(178-199) and 4.4-6 mol of TRH/mol of prepro-TRH-(160-169), respectively. By using the indirect immunofluorescence technique, prepro-TRH-(178-199) immunoreactive cell bodies were found in the paraventricular nucleus of the hypothalamus, and a dense plexus of immunopositive nerve terminals was observed in the external zone of the median eminence, in a distribution similar to that described for TRH. These studies demonstrate that prepro-TRH-(160-169) and prepro-TRH-(178-199) are, together with TRH, predominant storage forms of the TRH precursor in hypothalamus and spinal cord, being present in molar ratios corresponding to those expected for a nearly complete processing of the prohormone molecule. The presence of pro-TRH-connecting peptides in various brain regions, including the median eminence, suggests that these peptides might act as neuromodulators in the central nervous system and/or neuroendocrine signals at the pituitary level. In the olfactory lobes, prepro-TRH is processed differently since a C-terminally extended form of TRH, prepro-TRH-(172-199), is found as a major end product along with lower but significant amounts of prepro-TRH-(178-199) and prepro-TRH-(160-169). The striking difference in pro-TRH processing patterns among the various tissues examined suggests differential regulating mechanisms for TRH and/or TRH-related activities.

Amino Acid Sequence↗
PubMed2005

Modulation of effective connectivity by cognitive demand in phonological verbal fluency.

Verbal fluency is a classic neuropsychological measure of language production. Phonological verbal fluency involves the generation of words beginning with a specified letter, and its functional neuroanatomy is comprised of a distributed network of regions which is modulated by cognitive load. In order to investigate the functional relationship of these regions, the effective connectivity was analyzed with covariance structural equation modeling under conditions of varying cognitive load. Significant path coefficients were evident between the anterior cingulate, left middle frontal gyrus, and precuneus. The left middle frontal gyrus showed a facilitory projection to the precuneus which had a suppressive influence on anterior cingulate activation. With increasing cognitive demand, the left middle frontal projection to the precuneus became suppressive, and the path coefficient from the precuneus to the anterior cingulate showed a marked diminution in strength. The path analysis suggests that the lead-in process for letter verbal fluency may primarily involve an orthographic visual strategy. The marked changes in path coefficients with the increased cognitive load may reflect the greater demands placed on executive function. The significant changes in path coefficient values with increased cognitive demand indicate the importance of accounting for task difficulty not only in the interpretation of brain activation maps but also for effective connectivity measurements.

Adult↗
PubMedDate not supplied

Cholera toxin mapping of retinal projections in pigeons (Columbia livia), with emphasis on retinohypothalamic connections.

Anterograde transport of cholera toxin subunit B (CTb) was used to study the retinal projections in birds, with an emphasis on retinohypothalamic connections. Pigeons (Columbia livia) were deeply anesthetized and received unilateral intraocular injections of CTb. In addition to known contralateral retinorecipient regions, CTb-immunoreactive fibers and presumptive terminals were found in several ipsilateral regions, such as the nucleus of the basal optic root, ventral lateral geniculate nucleus, intergeniculate leaflet, nucleus lateralis anterior, area pretectalis, and nucleus pretectalis diffusus. In the hypothalamus, CTb-immunoreactive fibers were observed in at least two contralateral cell groups, a medial hypothalamic retinorecipient nucleus, and a lateral hypothalamic retinorecipient nucleus. To compare retinorecipient hypothalamic nuclei in pigeons with the mammalian suprachiasmatic nucleus, double-label experiments were conducted to study the existence of neurophysin-like immunoreactivity in the retinorecipient avian hypothalamus. The results showed that only cell bodies in the medial hypothalamic nucleus contained neurophysin-like immunoreactivity. The results demonstrate CTb to be a sensitive anterograde tracer and provide further anatomical information on the avian equivalent of the mammalian suprachiasmatic nucleus.

Animals↗
PubMed1993

Postoperative pulmonary flow dynamics after Fontan surgery: assessment with nuclear magnetic resonance velocity mapping.

OBJECTIVES: This study was performed to assess the value of nuclear magnetic resonance (NMR) velocity mapping for the measurement of pulmonary blood flow after Fontan surgery. BACKGROUND: Echocardiographic studies of pulmonary flow after Fontan surgery are not always satisfactory. The newly developed technique of NMR velocity mapping may contribute to the elucidation of the Fontan circulation. METHODS: At frequent intervals during the cardiac cycle, forward and backward flow volumes in the pulmonary arteries of nine volunteers were measured, summed and compared with right ventricular stroke volume to validate the velocity mapping technique. In 14 patients after Fontan surgery, assessment of pulmonary flow volumes enabled the evaluation of atriopulmonary and atrioventricular (AV) Fontan connections. The findings were correlated with precordial echocardiography. RESULTS: Validation of the NMR technique, obtained from volunteer experiments, showed a high correlation (r = 0.97) between right ventricular stroke volume and volumetric pulmonary stroke flow. In all patients with an atriopulmonary Fontan connection (n = 8), forward flow in the pulmonary artery was biphasic, similar to normal venous flow. Monophasic systolic pulmonary flow curves indicating right ventricle-dependent pulmonary blood flow were found in three of six patients with an AV Fontan connection. In the remaining three patients, the pulmonary flow pattern did not reflect right ventricular contraction. Measurement of flow velocity alone may give a false impression of forward flow and thus of right ventricular contribution. Pulmonary regurgitation was demonstrated in six of eight patients with an atriopulmonary connection. CONCLUSIONS: Nuclear magnetic resonance velocity mapping provides accurate and valuable information on pulmonary flow volume and velocity after Fontan surgery. The success of AV Fontan surgery can be deduced from the presence of a monophasic systolic pulmonary flow pattern as demonstrated by NMR velocity mapping. With NMR flow volume analysis, substantial pulmonary regurgitation occurring after atriopulmonary Fontan surgery can be measured.

Adolescent↗
PubMed2004

Context-dependent selection of visuomotor maps.

BACKGROUND: Behavior results from the integration of ongoing sensory signals and contextual information in various forms, such as past experience, expectations, current goals, etc. Thus, the response to a specific stimulus, say the ringing of a doorbell, varies depending on whether you are at home or in someone else's house. What is the neural basis of this flexibility? What mechanism is capable of selecting, in a context-dependent way an adequate response to a given stimulus? One possibility is based on a nonlinear neural representation in which context information regulates the gain of stimulus-evoked responses. Here I explore the properties of this mechanism. RESULTS: By means of three hypothetical visuomotor tasks, I study a class of neural network models in which any one of several possible stimulus-response maps or rules can be selected according to context. The underlying mechanism based on gain modulation has three key features: (1) modulating the sensory responses is equivalent to switching on or off different subpopulations of neurons, (2) context does not need to be represented continuously, although this is advantageous for generalization, and (3) context-dependent selection is independent of the discriminability of the stimuli. In all cases, the contextual cues can quickly turn on or off a sensory-motor map, effectively changing the functional connectivity between inputs and outputs in the networks. CONCLUSIONS: The modulation of sensory-triggered activity by proprioceptive signals such as eye or head position is regarded as a general mechanism for performing coordinate transformations in vision. The present results generalize this mechanism to situations where the modulatory quantity and the input-output relationships that it selects are arbitrary. The model predicts that sensory responses that are nonlinearly modulated by arbitrary context signals should be found in behavioral situations that involve choosing or switching between multiple sensory-motor maps. Because any relevant circumstancial information can be part of the context, this mechanism may partly explain the complex and rich behavioral repertoire of higher organisms.

Action Potentials↗
PubMed1992

Physical mapping of human loci homologous to the chicken nov proto-oncogene.

The human locus (novH) corresponding to the nov protooncogene overexpressed in avian nephroblastoma has been identified and mapped on chromosome 8q24.1. Another locus sharing homology with novH and corresponding to the connective tissue growth factor (CTGF) gene has also been mapped on chromosome 6q23.1. The chromosomal assignment of nov and CTGF proximal to c-myc and c-myb respectively is of interest because chromosomal abnormalities involving these regions have been associated with different human tumors including Wilms'.

Animals↗